Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model  

作　　者：Chun-kai HUANG Bi-yi CHEN Ang GUO Rong CHEN Yan-qi ZHU William KUTSCH KE Jiang HONG Long-sheng SONG 

机构地区：[1]Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China [2]Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA [3]Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA

出　　处：《Acta Pharmacologica Sinica》2016年第4期473-482,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the Scientific Research Foundation of Shanghai Jiao Tong University School of Medicine （No 12XJ3008, Jiang HONG）, the National Natural Science Foundation of China （No 81570293, Jiang HONG）, and the United States National Heart, Lung and Blood Institute （No R01 HL090905, Long-sheng SONG）,

摘　　要：Aim： Sildenafil, a phosphodiesterase 5 （PDE5） inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule （T-tubule） remodeling in left ventricular （LV） failure and thereby providing the therapeutic benefits. Methods： A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding （TAB）. One day after TAB, the mice received sildenafil （100 mg.kg1.d-1, sc） or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results： TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy （R2=0.74, P〈0.01） and global LV function （R2=0.47, P〈0.01）. Conclusion： Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure.Aim： Sildenafil, a phosphodiesterase 5 （PDE5） inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule （T-tubule） remodeling in left ventricular （LV） failure and thereby providing the therapeutic benefits. Methods： A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding （TAB）. One day after TAB, the mice received sildenafil （100 mg.kg1.d-1, sc） or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results： TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy （R2=0.74, P〈0.01） and global LV function （R2=0.47, P〈0.01）. Conclusion： Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure.

关 键 词：SILDENAFIL PDE5 inhibitor T-tubule pressure overload left ventricular remodeling left heart failure 

分 类 号：Q959.837[生物学—动物学] TS218[轻工技术与工程—粮食、油脂及植物蛋白工程]